Soluble TREM2 levels associate with conversion from mild cognitive impairment to Alzheimer’s disease

Abstract

BACKGROUND Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) plays an important role in the clearance of pathological amyloid-β (Aβ) in Alzheimer’s disease (AD). This study aimed to explore sTREM2 as a central and peripheral predictor of the conversion from mild cognitive impairment (MCI) to AD. METHODS sTREM2 and Aβ 1–42 levels in cerebrospinal fluid (CSF) and florbetapir-PET (AV45) images were analyzed for healthy control (HCs), patients with MCI, and patients with AD from the ADNI database. Peripheral plasma sTREM2 and Aβ 1–42 levels were determined for our Neurology database of Ruijin Hospital for Alzheimer’s Disease (NRHAD) cohort, and patients with MCI were reevaluated at follow-up visits to assess for progression to AD. The association between CSF and plasma sTREM2 levels was analyzed in data from the Chinese Alzheimer’s Biomarker and Lifestyle (CABLE) database. RESULTS The results showed that patients with MCI who had low levels of CSF sTREM2 and Aβ 1–42 were more likely to develop AD. Among participants with positive Aβ deposition, as assessed by AV45 imaging, elevated CSF sTREM2 levels were associated with a decreased risk of MCI-to-AD conversion. Meanwhile, in the NRHAD cohort, individuals in the MCI group with high sTREM2 levels in plasma were at a greater risk for AD, whereas low Aβ 1–42 with high sTREM2 levels in plasma were associated with a faster cognitive decline. In addition, CSF sTREM2 levels were highly correlated with plasma sTREM2 levels in the CABLE database. CONCLUSION These findings suggest that sTREM2 may be useful as a potential predictive biomarker of MCI-to-AD conversion. FUNDING This study was supported by grants from the National Natural Science Foundation of China (grant nos. 82001341, 82071415, 81873778, and 82201392); the Shanghai Sailing Program (grant no. 22YF1425100); and the China Postdoctoral Science Foundation funded project (grant no. 2021M702169).

Association of Chronic Pain with Biomarkers of Neurodegeneration, Microglial Activation, and Inflammation in Cerebrospinal Fluid and Impaired Cognitive Function

“…However, our study is the first to suggest a link between neuronal damage and neurodegeneration with microglial activation in chronic pain states. Additionally, we observed that the difference in sTREM2 CSF levels between chronic pain states in the SNAP group were close to the differences reported between healthy controls and MCI or AD patients 21,30 . Because the CSF levels of sTREM2 and biomarkers of neurodegeneration were analyzed from the same aliquot in ADNI, we were not able to determinate whether microglial activation preceded neuronal damage.…”

Exercise suppresses neuroinflammation for alleviating Alzheimer’s disease

“…TREM2 levels in CSF reveal the reduction before AD and the increase in early AD, and the final decrease again in late AD [69]. Plasma GFAP can more accurately reflect the changes in Aβ burden (not Tau protein) and disease severity in pre-symptomatic AD when compared with GFAP and TREM2 in CSF [70][71][72]. At the same time, TREM2 levels in CSF are closely related to Tau protein [73].…”

“…At the same time, TREM2 levels in CSF are closely related to Tau protein [ 73 ]. In addition, a biomarker analysis of healthy elderly, MCI patients, and AD patients has found that MCI patients with low levels of TREM2 in CSF or high levels of plasma TREM2 are more likely to accelerate the progression of AD [ 71 ]. In AD and other neurodegenerative diseases, the function of TREM2-mediated activation of microglia depends on the stage of disease progression and the type of microglia [ 74 ].…”

Intrathecal Pseudodelivery of Drugs in the Therapy of Neurodegenerative Diseases: Rationale, Basis and Potential Applications

“…Levels of sTREM2 in CSF fall prior to AD clinical onset, rise in early AD, and fall again in late AD. Subjects with higher sTREM2 levels in CSF progress more slowly into and through AD than do subjects with lower sTREM2 levels, suggesting that sTREM2 may protect against AD [ 25 , 26 , 27 , 28 ].…”